Biological mechanisms of many diseases have been clarified by microscopic examination of tissue specimens. Histopathological examination has also permitted the development of effective medical treatments for a variety of illnesses. In standard anatomical pathology, a diagnosis is made on the basis of cell morphology and staining characteristics. Tumor specimens, for example, can be examined to characterize the tumor type and predict the aggressiveness of the tumor. Although this microscopic examination and classification of tumors has improved medical treatment, the microscopic appearance of a tissue specimen stained by standard methods (such as hematoxylin and eosin) can often reveal only a limited amount of diagnostic or molecular information.
Recent advances in molecular medicine have provided an even greater opportunity to understand the cellular mechanisms of disease, and select appropriate treatments with the greatest likelihood of success. Some hormone dependent breast tumor cells, for example, have an increased expression of estrogen receptors on their cell surfaces, which indicates that the patient from whom the tumor was taken will likely respond to certain anti-estrogenic drug treatments. Other diagnostic and prognostic cellular changes include the presence of tumor specific cell surface antigens (as in melanoma), the production of embryonic proteins (such as α-fetoprotein in liver cancer and carcinoembryonic glycoprotein antigen produced by gastrointestinal tumors), and genetic abnormalities (such as activated oncogenes in tumors). A variety of techniques have evolved to detect the presence of these cellular abnormalities, including immunophenotyping with monoclonal antibodies, in situ hybridization with probes, and DNA amplification using the polymerase chain reaction (PCR).
The development of new molecular markers of clinical importance has been impeded by the slow and tedious process of evaluating biomarkers in large numbers of clinical specimens. For example, hundreds of tissue specimens representing different stages of tumor progression have to be evaluated before the importance of a given marker can be assessed. Since the number of antibodies, as well as probes for mRNA or DNA targets is increasing rapidly, only a small fraction of these can ever be tested in large numbers of clinical specimens.
Various methods have been explored to prepare samples of multiple tissues or nucleic acids on one slide or plate.